{"doi":"10.1002/ange.202212636","title":"Apolipoprotein E Recognizes Alzheimer's Disease Associated 3‐<i>O</i> Sulfation of Heparan Sulfate","abstract":"Abstract Apolipoprotein E (ApoE)’s ϵ4 alle is the most important genetic risk factor for late onset Alzheimer's Disease (AD). Cell‐surface heparan sulfate (HS) is a cofactor for ApoE/LRP1 interaction and the prion‐like spread of tau pathology between cells. 3‐ O ‐sulfo (3‐ O ‐S) modification of HS has been linked to AD through its interaction with tau, and enhanced levels of 3‐ O ‐sulfated HS and 3‐ O ‐sulfotransferases in the AD brain. In this study, we characterized ApoE/HS interactions in wildtype ApoE3, AD‐linked ApoE4, and AD‐protective ApoE2 and ApoE3‐Christchurch. Glycan microarray and SPR assays revealed that all ApoE isoforms recognized 3‐ O ‐S. NMR titration localized ApoE/3‐ O ‐S binding to the vicinity of the canonical HS binding motif. In cells, the knockout of HS3ST1‐a major 3‐ O sulfotransferase‐reduced cell surface binding and uptake of ApoE. 3‐ O ‐S is thus recognized by both tau and ApoE, suggesting that the interplay between 3‐ O ‐sulfated HS, tau and ApoE isoforms may modulate AD risk.","journal":"Angewandte Chemie","year":2023,"id":368544,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9616,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":880633,"name":"Yanan Zhu","orcid":"0000-0003-0465-5146","position":1,"is_corresponding":false},{"id":288983,"name":"Guowei Su","orcid":"0000-0003-2668-9275","position":2,"is_corresponding":false},{"id":230874,"name":"Jing Zhao","orcid":"0000-0002-4520-6307","position":3,"is_corresponding":false},{"id":1059927,"name":"Ashely Canning","orcid":null,"position":4,"is_corresponding":false},{"id":708623,"name":"James M. Gibson","orcid":"0000-0002-9378-0135","position":5,"is_corresponding":false},{"id":659442,"name":"Xuehong Song","orcid":null,"position":6,"is_corresponding":false},{"id":420148,"name":"Eduardo Stancanelli","orcid":"0000-0002-6006-2209","position":7,"is_corresponding":false},{"id":288975,"name":"Yongmei Xu","orcid":"0000-0002-3756-581X","position":8,"is_corresponding":false},{"id":233177,"name":"Fuming Zhang","orcid":"0000-0003-2803-3704","position":9,"is_corresponding":false},{"id":286697,"name":"Robert J. Linhardt","orcid":"0000-0003-2219-5833","position":10,"is_corresponding":false},{"id":288986,"name":"Jian Liu","orcid":"0000-0001-8552-1400","position":11,"is_corresponding":false},{"id":603500,"name":"Lianchun Wang","orcid":"0000-0003-1454-2719","position":12,"is_corresponding":false},{"id":255565,"name":"Chunyu Wang","orcid":"0000-0001-5165-7959","position":13,"is_corresponding":false},{"id":670886,"name":"Dylan Mah","orcid":"0000-0002-7734-6101","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T01:15:24.517012Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}